Researchers at Texas Children’s Duncan Neurological Research Institute and Baylor College of Medicine have found a new way to raise the level of a brain protein that is low in Rett syndrome. Their study, published in Science Translational Medicine, explains how removing a small part of the gene can make the brain produce more of the helpful protein.
Why the MECP2 Gene Matters
Rett syndrome is caused by changes in the MECP2 gene. This gene tells the brain how to turn many other genes on or off. When the gene is broken, the protein it makes – called MeCP2 – is missing or works badly. Without enough MeCP2, brain cells cannot communicate properly.
Mouse experiments have shown that adding a healthy MeCP2 protein can improve Rett‑like symptoms. Even adding a partially working version of the protein can help mice breathe, move, and live longer.
Two Versions of the Same Protein
Our cells actually make two slightly different forms of MeCP2, named E1 and E2. Both come from the same gene, but they are built using different pieces of the genetic recipe. The E1 version is the most common in the brain, while E2 is made in smaller amounts.
Scientists noticed that people with Rett syndrome never have mutations in the part that creates E2. Only changes that affect E1 cause the disease. This clue suggested that increasing the E1 form could be beneficial.
Removing the “e2” Piece
The team decided to try a simple trick: cut out the tiny “e2” segment from the gene. In normal mice, this edit raised the total MeCP2 protein by about 50‑60 percent.
Next, they used cells taken from children with Rett syndrome. These cells carried faulty MECP2 genes that made too little protein. Deleting the same “e2” piece caused the cells to make much more MeCP2. Depending on how severe the original mutation was, the cells began to look and act more like healthy brain cells.
Testing a Drug‑Like Molecule
The researchers also tried a laboratory molecule called a morpholino. This molecule blocks the cell’s ability to read the “e2” part, effectively skipping it. When given to mice, the morpholino boosted MeCP2 levels in the brain.
Although morpholinos are too toxic for real patients, the result proves that a drug that blocks the e2 segment could one day raise MeCP2 safely. Similar approaches, such as antisense oligonucleotides, are already used for other genetic diseases and might be adapted for Rett syndrome.
What Comes Next?
This work gives scientists a clear roadmap for a new treatment strategy. By nudging brain cells to make more of the helpful E1 protein, we may be able to lessen the symptoms of Rett syndrome.
The study was funded by the National Institutes of Health, the Howard Hughes Medical Institute, and several other research foundations.